The Authors Reply
Authors: Vaibhav Keskar, Eric McArthur, Ron Wald, Ziv Harel, Deborah Zimmerman, Amber Molnar, Amit X. Garg, Ngan Lam, Megan K. McCallum, Sarah E. Bota, Jeffrey Perl, Manish M. Sood
Journal: Kidney International (2017)

We would like to commend Dr. Brancaccio et al. for their insightful comments1Brancaccio D. Neri L. Bellocchio F. et al.Warfarin in CKD patients with atrial fibrillation.Kidney Int. 2017; 92: 766-767Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar regarding the conundrum of anticoagulation for atrial fibrillation with advanced chronic kidney disease.2Keskar V. McArthur E. Wald R. et al.The association of anticoagulation, ischemic stroke, and hemorrhage in elderly adults with chronic kidney disease and atrial fibrillation.Kidney Int. 2017; 91: 928-936Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar We mainly agree with their comments and plan to address risk stratification and international normalized ratio–related queries in the near future. We agree that better means to identify anticoagulated patients at high risk of bleeding events are required and strategies of mitigation need to be identified.3Sood M.M. Bota S.E. McArthur E. et al.The three-year incidence of major hemorrhage among older adults initiating chronic dialysis.Can J Kidney Health Dis. 2014; 1: 1-10Crossref PubMed Scopus (1) Google Scholar Recent studies demonstrate that high international normalized ratio variability and/or less time in the therapeutic range are associated with bleeding events in chronic kidney disease.4Szummer K. Gasparini A. Eliasson S. et al.Time in therapeutic range and outcomes after warfarin initiation in newly diagnosed atrial fibrillation patients with renal dysfunction.J Am Heart Assoc. 2017 Mar 1; 6Crossref PubMed Scopus (57) Google Scholar This is exacerbated by vitamin K deficiency common in chronic kidney disease and end-stage kidney disease.5Holden R.M. Booth S.L. Vascular calcification in chronic kidney disease: the role of vitamin K.Nat Clin Pract Nephrol. 2007; 3: 522-523Crossref PubMed Scopus (38) Google Scholar At present, numerous hemorrhage risk scores derived from the general population are available, with poor discrimination in patients with a low estimated glomerular filtration rate.6McAlister F.A. Wiebe N. Jun M. et al.Are existing risk scores for nonvalvular atrial fibrillation useful for prediction or risk adjustment in patients with chronic kidney disease?.Can J Cardiol. 2017; 33: 243-252Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Further areas of exploration include alternative dosing strategies, coadministration of vitamin K, and the role of prophylactic proton pump inhibitors. One point of disagreement with the authors (also echoed in the accompanying editorial) is whether observational studies of efficacy/harm are required. Subgroups, such as the elderly, in whom the likelihood of a trial being conducted is low, are the ideal population to examine with observational study designs, and studies like ours may represent the only direct evidence available. The agreement between well-conducted observational research and randomized, controlled trials is well established.7Anglemyer A. Horvath H.T. Bero L. Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials.Cochrane Database Syst Rev. 2014 Apr 29; : MR000034PubMed Google Scholar Warfarin in CKD patients with atrial fibrillationKidney InternationalVol. 92Issue 3PreviewKeskar et al.1 evaluated the association of oral anticoagulation in cardiovascular endpoints and all-cause mortality in a historical cohort of 6544 patients with reduced renal function (estimated glomerular filtration rate <45 ml/min per 1.73 m2) and atrial fibrillation. Full-Text PDF Open ArchiveThe association of anticoagulation, ischemic stroke, and hemorrhage in elderly adults with chronic kidney disease and atrial fibrillationKidney InternationalVol. 91Issue 4PreviewThe utility of anticoagulants for ischemic stroke prophylaxis in elderly patients with chronic kidney disease (CKD) and atrial fibrillation remains uncertain. In this population-based retrospective cohort study, we determined the association of anticoagulant use with ischemic stroke or hemorrhage in elderly patients (66 years and older) with advanced chronic kidney disease (eGFR under 45 ml/min/1.73m2) and atrial fibrillation. We followed 6,544 patients with CKD and new onset atrial fibrillation, of whom 1,475 filled a prescription for an anticoagulant. Full-Text PDF Open Archive